Comparative Efficacy and Safety of Oral Versus Intravaginal Metronidazole for the Treatment of Bacterial Vaginosis: A Systematic Review and Meta-Analysis.

Background: Although oral and intravaginal metronidazole (MNZ) are recommended as the standard treatments for bacterial vaginosis (BV), the optimal route of administration remains controversial. Oral MNZ is effective but often leads to gastrointestinal side effects and thus reduces patient adherence. Intravaginal MNZ may offer similar efficacy with improved tolerability; however, comprehensive evidence is needed to guide treatment choices. This study aimed to compare oral and intravaginal MNZ for BV treatment.

Methods: In this systematic review and meta-analysis of randomized controlled trials (RCTs), the primary outcomes were the clinical and microbiological cure rates, and the secondary outcome was the incidence of adverse gastrointestinal events. Relevant studies published until March 2025 were identified through database searches (PubMed, Web of Science, Scopus, and Ichushi). Data were synthesized using risk ratios (RRs) and 95% confidence intervals (CIs) with random-effects models.

Results: Seven RCTs, including 697 patients, were analyzed. Clinical cure rates were equivalent between oral and intravaginal MNZ groups (pooled RR, 1.00; 95% CI 0.94-1.06; p=0.90). Microbiological cure rates also showed no significant difference (RR=0.95; 95% CI 0.75-1.71; p=0.66). Gastrointestinal side effects were significantly more frequent in the oral MNZ group than in the intravaginal MNZ group (RR=2.29; 95% CI 1.57-3.35; p<0.001). Intravaginal MNZ was associated with better tolerability than oral MNZ.

Conclusion: Oral and intravaginal MNZ offer similar efficacies for BV treatment; however, intravaginal administration reduces systemic side effects and may improve adherence. Treatment should be individualized on the basis of patient preferences, side effect profiles, and accessibility.